MEPSA: Minimum energy pathway analysis for energy landscapes

From conformational studies to atomistic descriptions of enzymatic reactions, potential and free energy landscapes can be used to describe biomolecular systems in detail. However, extracting the relevant data of complex 3D energy surfaces can sometimes be laborious. In this article, we present MEPSA (Minimum Energy Path Surface Analysis), a cross-platform user friendly tool for the analysis of energy landscapes from a transition state theory perspective. Some of its most relevant features are: identification of all the barriers and minima of the landscape at once, description of maxima edge profiles, detection of the lowest energy path connecting two minima and generation of transition state theory diagrams along these paths. In addition to a built-in plotting system, MEPSA can save most of the generated data into easily parseable text files, allowing more versatile uses of MEPSA's output such as the generation of molecular dynamics restraints from a calculated path.Grant IPT2011-0964-900000 (Government of Spain).Peer Reviewe

Two-step ATP-driven opening of cohesin head.

The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the “head” structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: i) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events. Our study suggests that the cohesin ring opening is triggered by a sequential activation of the ATP sites in which ATP hydrolysis at the Smc1A site induces ATPase activity at the Smc3 site. Our analysis also provides an explanation for the effect of pathogenic variants related to cohesinopathies and cancer.post-print4709 K

COMPARACIÓN DE LAS PRINCIPALES MOSCAS NECRÓFAGAS ATRAÍDAS POR HÍGADOS HUMANOS EN ESTADO DE DESCOMPOSICIÓN, EXPUESTOS A DIFERENTES INTERVALOS DE TIEMPO, EN UN ÁREA URBANA DE LA PROVINCIA DE PANAMÁ.

Four samples of human´s livers of approximately 150 – 200 g. were obtained from the Judicial Mortuary of Panama. The livers were used at different interval from 12, 24, 48, 72 and 96 hours of decomposition. The flies were captured during 3 hours with intervals of 10, 15 and 20 min, until the 3 hours sampling was completed. A total amount of 1 003 flies were captured, distributed in 3 families: Calliphoridae, Sarcophagide y Muscidae. To capture 11 species, the more abundant species corresponded to Chrysomya megacephala, with 464 specimens, Lucila cuprina, with 117 specimens, Lucilia sericata, with 55 specimens and Lucilia eximia, with 47 specimens. The purpose of this research was knew the colonization of human liver, exposed at different time intervals in an urban area of the province of Panama.Se obtuvieron cuatro muestras de hígados humanos, de aproximadamente de 150 a 200 g. de la Morgue Judicial de Panamá. Los tejidos se expusieron a intervalos de tiempo que iban desde las primeras 12 horas, incluyendo las 24, 48, 72 y hasta 96 horas de descomposición. Las capturas de las moscas se realizaron durante tres horas continuas. En total se capturaron 1003 ejemplares, distribuidos en tres familias y 11 especies: Calliphoridae, Sarcophagidae y Muscida. La familia que mayormente atrapada en los tejidos fue la Calliphoridae seguida de la Sarcophagidae. Las especies más abundantes en el área correspondió a Chrysomya megacephala, con 464 ejemplares y Lucilia cuprina con 117 ejemplares, seguido de Lucilia sericata con 55 ejemplares y Lucilia eximia con 47 ejemplares. El objetivo de esta investigación fue conocer las principales especies de moscas necrófagas que arriban a los hígados humanos, expuestos a diferentes intervalos, en un área urbana de la provincia de Panamá

Tetanus toxin Hc fragment induces the formation of ceramide platforms and protects neuronal cells against oxidative stress

Tetanus toxin (TeTx) is the protein, synthesized by the anaerobic bacteria Clostridium tetani, which causes tetanus disease. TeTx gains entry into target cells by means of its interaction with lipid rafts, which are membrane domains enriched in sphingomyelin and cholesterol. However, the exact mechanism of host membrane binding remains to be fully established. In the present study we used the recombinant carboxyl terminal fragment from TeTx (Hc-TeTx), the domain responsible for target neuron binding, showing that Hc-TeTx induces a moderate but rapid and sustained increase in the ceramide/sphingomyelin ratio in primary cultures of cerebellar granule neurons and in NGF-differentiated PC12 cells, as well as induces the formation of ceramide platforms in the plasma membrane. The mentioned increase is due to the promotion of neutral sphingomyelinase activity and not to the de novo synthesis, since GW4869, a specific neutral sphingomyelinase inhibitor, prevents neutral sphingomyelinase activity increase and formation of ceramide platforms. Moreover, neutral sphingomyelinase inhibition with GW4869 prevents Hc-TeTx-triggered signaling (Akt phosphorylation), as well as the protective effect of Hc-TeTx on PC12 cells subjected to oxidative stress, while siRNA directed against nSM2 prevents protection by Hc-TeTx of NSC-34 cells against oxidative insult. Finally, neutral sphingomyelinase activity seems not to be related with the internalization of Hc-TeTx into PC12 cells. Thus, the presented data shed light on the mechanisms triggered by TeTx after membrane binding, which could be related with the events leading to the neuroprotective action exerted by the Hc-TeTx fragment

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

A practical quantum mechanics molecular mechanics method for the dynamical study of reactions in biomolecules (Conference Paper)

Quantum mechanics/molecular mechanics (QM/MM) methods are excellent tools for the modeling of biomolecular reactions. Recently, we have implemented a new QM/MM method (FIREBALL/AMBER), which combines an efficient density functional theory method (FIREBALL) and a well-recognized molecular dynamics package (AMBER), offering an excellent balance between accuracy and sampling capabilities. Here, we present a detailed explanation of the FIREBALL method and FIREBALL/AMBER implementation. We also discuss how this tool can be used to analyze reactions in biomolecules using steered molecular dynamics simulations. The potential of this approach is shown by the analysis of a reaction catalyzed by the enzyme triose-phosphate isomerase (TIM). The conformational space and energetic landscape for this reaction are analyzed without a priori assumptions about the protonation states of the different residues during the reaction. The results offer a detailed description of the reaction and reveal some new features of the catalytic mechanism. In particular, we find a new reaction mechanism that is characterized by the intramolecular proton transfer from O1 to O2 and the simultaneous proton transfer from Glu 165 to C2.Ministerio de Economía y Competitividad (MINECO), projects MAT2014-59966-R (J.O.) and IPT2011- 0964-900000 (P.G-P.). Work at Biomol-Informatics was partially financed by the European Social Fund.Peer Reviewe

Effect of water-DNA interactions on elastic properties of DNA self-assembled monolayers

DNA-water interactions have revealed as very important actor in DNA mechanics, from the molecular to the macroscopic scale. Given the particularly useful properties of DNA molecules to engineer novel materials through self-assembly and by bridging organic and inorganic materials, the interest in understanding DNA elasticity has crossed the boundaries of life science to reach also materials science and engineering. Here we show that thin films of DNA constructed through the self-assembly of sulfur tethered ssDNA strands demonstrate a Young's modulus tuning range of about 10 GPa by simply varying the environment relative humidity from 0% up to 70%. We observe that the highest tuning range occurs for ssDNA grafting densities of about 3.5 × 10 molecules/cm , where the distance between the molecules maximizes the water mediated interactions between the strands. Upon hybridization with the complementary strand, the DNA self-assembled monolayers significantly soften by one order of magnitude and their Young's modulus dependency on the hydration state drastically decreases. The experimental observations are in agreement with molecular dynamics simulations.Spanish Science Ministry (MINECO) through project MAT2015-66904-R and by European Research Council through NANOFORCELLS project (ERC-StG-2011-278860).Peer Reviewe

Adsorption orientations and immunological recognition of antibodies on graphene

Large-scale molecular dynamics (MD) simulations and atomic force microscopy (AFM) in liquid are combined to characterize the adsorption of Immunoglobulin G (IgG) antibodies over a hydrophobic surface modeled with a three-layer graphene slab. We consider explicitly the water solvent, simulating systems with massive sizes (up to 770000 atoms), for four different adsorption orientations. Protocols based on steered MD to speed up the protein diffusion stage and to enhance the dehydration process are combined with long simulation times (>150 ns) in order to make sure that the final adsorption states correspond to actual stable configurations. Our MD results and the AFM images demonstrate that the IgG antibodies are strongly adsorbed, do not unfold, and retain their secondary and tertiary structures upon deposition. Statistical analysis of the AFM images shows that many of the antibodies adopt vertical orientations, even at very small coverages, which expose at least one Fab binding site for recognition events. Single molecule force spectroscopy experiments demonstrate the immunological response of the deposited antibodies by recognizing its specific antigens. The above properties together with the strong anchoring and preservation of the secondary structure, make graphene an excellent candidate for the development of immunosensors.We thank the financial support from the Spanish MINECO (projects Consolider Force-For-Future CSD2010-00024, MAT2011-023627, MAT2013-44858-R, FIS2012-36113-C03-03, and MAT2014-54484-P), and from Comunidad de Madrid (S2009/MAT-1467)

Data - Generating Antiaromaticity by Thermally-selective Skeletal Rearrangements at Interfaces

STM-ncAFM from IMDEA Nanociencia Institute and CATRIN under ultra-high vacuum conditions at 4K, acquired between 2018 and 03.2023*.txt *.jpg *.docx files, *.WSxM files can be opened with Origi